Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial

OBJECTIVES: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD).

DESIGN: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard).

SETTING: Internet-based application.

PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care.

INTERVENTIONS: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes.

MAIN OUTCOME MEASURES: Primary outcome-correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions.

RESULTS: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists.

CONCLUSIONS: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals.

TRIAL REGISTRATION NUMBER: ISRCTN07479761; pre-results registration.

Mixture of time-dependent growth models with an application to blue swimmer crab length-frequency data

Understanding how aquatic species grow is fundamental in fisheries because stock assessment often relies on growth dependent statistical models. Length-frequency-based methods become important when more applicable data for growth model estimation are either not available or very expensive. In this article, we develop a new framework for growth estimation from length-frequency data using a generalized von Bertalanffy growth model (VBGM) framework that allows for time-dependent covariates to be incorporated. A finite mixture of normal distributions is used to model the length-frequency cohorts of each month with the means constrained to follow a VBGM. The variances of the finite mixture components are constrained to be a function of mean length, reducing the number of parameters and allowing for an estimate of the variance at any length. To optimize the likelihood, we use a minorization–maximization (MM) algorithm with a Nelder–Mead sub-step. This work was motivated by the decline in catches of the blue swimmer crab (BSC) (Portunus armatus) off the east coast of Queensland, Australia. We test the method with a simulation study and then apply it to the BSC fishery data.

Branching dendrites with resonant membrane: a "sum-over-trips" approach

Dendrites form the major components of neurons. They are complex branching structures that receive and process thousands of synaptic inputs from other neurons. It is well known that dendritic morphology plays an important role in the function of dendrites. Another important contribution to the response characteristics of a single neuron comes from the intrinsic resonant properties of dendritic membrane. In this paper we combine the effects of dendritic branching and resonant membrane dynamics by generalising the "sum-over-trips" approach [Abbott, L.F., Fahri, E., Gutmann, S.: The path integral for dendritic trees. Biological Cybernetics 66, 49--60 (1991)]. To illustrate how this formalism can shed light on the role of architecture and resonances in determining neuronal output we consider dual recording and reconstruction data from a rat CA1 hippocampal pyramidal cell. Specifically we explore the way in which an $I_{h}$ current contributes to a voltage overshoot at the soma.

Shifting Processes with Cyclically Exchangeable Increments at Random

International audience

Age-Dependent Fragility and Life-Cycle Cost Analysis of Timber and Steel Distribution Poles Subjected to Hurricanes

Power distribution systems are susceptible to extreme damage from natural hazards especially hurricanes. Hurricane winds can knock down distribution poles thereby causing damage to the system and power outages which can result in millions of dollars in lost revenue and restoration costs. Timber has been the dominant material used to support overhead lines in distribution systems. Recently however, utility companies have been searching for a cost-effective alternative to timber poles due to environmental concerns, durability, high cost of maintenance and need for improved aesthetics. Steel has emerged as a viable alternative to timber due to its advantages such as relatively lower maintenance cost, light weight, consistent performance, and invulnerability to wood-pecker attacks. Both timber and steel poles are prone to deterioration over time due to decay in the timber and corrosion of the steel. This research proposes a framework for conducting fragility analysis of timber and steel poles subjected to hurricane winds considering deterioration of the poles over time. Monte Carlo simulation was used to develop the fragility curves considering uncertainties in strength, geometry and wind loads. A framework for life-cycle cost analysis is also proposed to compare the steel and timber poles. The results show that steel poles can have superior reliability and lower life-cycle cost compared to timber poles, which makes them suitable substitutes.

Pertussis booster vaccine for adolescents and young adults in São Paulo, Brazil

OBJECTIVE: To develop a model to assess different strategies of pertussis booster vaccination in the city of São Paulo. METHODS: A dynamic stationary age-dependent compartmental model with waning immunity was developed. The "Who Acquires Infection from Whom" matrix was used to modeling age-dependent transmission rates. There were tested different strategies including vaccine boosters to the current vaccination schedule and three of them were reported: (i) 35% coverage at age 12, or (ii) 70% coverage at age 12, and (iii) 35% coverage at age 12 and 70% coverage at age 20 at the same time. RESULTS: The strategy (i) achieved a 59% reduction of pertussis occurrence and a 53% reduction in infants while strategy (ii) produced 76% and 63% reduction and strategy (iii) 62% and 54%, respectively. CONCLUSION: Pertussis booster vaccination at age 12 proved to be the best strategy among those tested in this study as it achieves the highest overall reduction and the greatest impact among infants who are more susceptible to pertussis complications.

Factors of poor prognosis of visceral leishmaniasis among children under 12 years of age. A retrospective monocentric study in Belo Horizonte, State of Minas Gerais, Brazil, 2001-2005

INTRODUTION: A major concern with the visceral leishmaniasis (VL) is its high lethality rate, even with proper treatment. Low age, prior malnutrition, disease duration prior to diagnosis, severe anemia, fever for more than 60 days, diarrhea and jaundice are known poor prognostic factors. The goals of this study are to describe the clinical and laboratory characteristics of VL among children under 12 years of age and to identify the factors associated with VL poor outcome. METHODS: Two hundred and fifty children under 12 years of age with confirmed VL admitted to Hospital João Paulo II (FHEMIG), Belo Horizonte, Brazil, between January 2001 and December 2005 were evaluated retrospectively. The primary outcome was the poor clinical evolution: sepsis, and/or pneumonia, and/or urinary tract infection, and/or of bleeding (expect epistaxis), and/or severe neutropenia (neutrophil < 500 cells/mm3). Odds ratio (crude and adjusted) and its 95% confidence interval for each variable were calculated. Values less than 0.05 were considered significant. RESULTS: Average age was 3.3 years (3.6 months-11.6 years), 71.2% were younger than 5 years and 47.2% lived in Metropolitan Area of Belo Horizonte. The mean fatality rate was 3.6%. Sixty-six (26.4%) patients presented poor evolution. After a multivariate analysis, age <18 months, abnormal respiratory physical examination on hospital admission, and platelets <85,000/mm3 remained associated with increased chance of poor evolution. CONCLUSIONS: The results suggest that patients aged between 12 and 18 months, with platelet counts bellow 85,000/mm3, and respiratory abnormalities at admission should be considered potentially severe.

Effect of age and gender on citalopram and desmethylcitalopram steady-state plasma concentrations in adults and elderly depressed patients.

The effect of aging on steady-state plasma concentrations of citalopram (CIT) and desmethylcitalopram (DCIT) was investigated in 128 depressive patients treated with 10-80 mg/day CIT. They were separated into three groups, with age up to 64 years (mean age+/-S.D.: 47+/-12 years; n=48), between 65 and 79 years (72+/-1 years; n=57), and from 80 years or older (84+/-1 years; n=23). Body mass index (BMI), renal and hepatic functions were similar in the three groups. A large interindividual variability of plasma levels of CIT (16-fold) and DCIT (12-fold) was measured for a given dose. The mean plasma levels of CIT corrected for a 20 mg daily dose were 55% higher in the very elderly (>=80 years) patients (65+/-30 ng/ml; p<0.001) and 38% higher in the elderly (65-79 years) patients (58+/-24 ng/ml; p<0.001) when compared to the adult patients (42+/-17 ng/ml). DCIT mean plasma level was 38% higher (p<0.05) in the group of very elderly patients (22+/-10 ng/ml) when compared to the adult patients (16+/-9 ng/ml). As a consequence, the mean plasma concentration of CIT+DCIT was 48% higher in the very elderly patients (86+/-36 ng/ml; p<0.001) and 33% higher in the elderly patients (77+/-28 ng/ml; p<0.001) when compared to the adult patients (58+/-21 ng/ml). Age correlated significantly with CIT (r=0.43, p<0.001), DCIT (r=0.28, p<0.01), and CIT+DCIT plasma levels (r=0.44, p<0.001), and thus accounts for 18% of the variability of CIT plasma levels, with no influence of gender. The recommended dose reduction of CIT in elderly patients seems therefore justified.

Less Conservative Control Design for Linear Systems with Polytopic Uncertainties via State-Derivative Feedback

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Configuration-Dependent Diffusion Dynamics of Downhill and Two-State Protein Folding

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Configuration-dependent diffusion can shift the kinetic transition state and barrier height of protein folding

We show that diffusion can play an important role in protein-folding kinetics. We explicitly calculate the diffusion coefficient of protein folding in a lattice model. We found that diffusion typically is configuration- or reaction coordinate-dependent. The diffusion coefficient is found to be decreasing with respect to the progression of folding toward the native state, which is caused by the collapse to a compact state constraining the configurational space for exploration. The configuration- or position-dependent diffusion coefficient has a significant contribution to the kinetics in addition to the thermodynamic free-energy barrier. It effectively changes (increases in this case) the kinetic barrier height as well as the position of the corresponding transition state and therefore modifies the folding kinetic rates as well as the kinetic routes. The resulting folding time, by considering both kinetic diffusion and the thermodynamic folding free-energy profile, thus is slower than the estimation from the thermodynamic free-energy barrier with constant diffusion but is consistent with the results from kinetic simulations. The configuration- or coordinate-dependent diffusion is especially important with respect to fast folding, when there is a small or no free-energy barrier and kinetics is controlled by diffusion. Including the configurational dependence will challenge the transition state theory of protein folding. The classical transition state theory will have to be modified to be consistent. The more detailed folding mechanistic studies involving phi value analysis based on the classical transition state theory also will have to be modified quantitatively.

American visceral leishmaniasis: Factors associated with lethality in the state of São Paulo, Brazil

Objectives. To identify factors associated with death in visceral leishmaniasis (VL) cases. Patients and Methodology. We evaluated prognostic factors for death from VL in São Paulo state, Brazil, from 1999 to 2005. A prognostic study nested in a clinical cohort was carried out by data analysis of 376 medical files. A comparison between VL fatal cases and survivors was performed for clinical, laboratory, and biological features. Association between variables and death was assessed by univariate analysis, and the multiple logistic regression model was used to determine adjusted odds ratio for death, controlling confounding factors. Results. Data analysis identified 53 fatal cases out of 376 patients, between 1999 and 2005 in São Paulo state. Lethality was 14.1 (53/376), being higher in patients older than fifty years. The main causes of death were sepsis, bleeding, liver failure, and cardiotoxicity due to treatment. Variables significantly associated with death were severe anemia, bleeding, heart failure, jaundice, diarrhea, fever for more than sixty days, age older than fifty years, and antibiotic use. Conclusion. Educational health measures are needed for the general population and continuing education programs for health professionals working in the affected areas with the purpose of identifying and treating early cases, thus preventing the disease evolution towards death. © 2012 Geraldine Madalosso et al.

Needs of Massachusetts' older citizens, with special reference to State programs and services. [Report]

Bibliography: p. 212-222.

Study of neutral Fe(III) complexes of pyridoxal-N-substituted thiosemicarbazone with desolvation induced spin-state transformation above room temperature

The preparation and characterization of two new neutral ferric complexes with desolvation-induced discontinuous spin-state transformation above room temperature are reported. The compounds, Fe(Hthpy)(thpy).CH3OH.3H2O (1) and Fe(Hmthpy)(mthpy).2H2O (2), are low-spin (LS) at room temperature and below, whereas their nonsolvated forms are high-spin (HS), exhibiting zero-field splitting. In these complexes, Hthpy, Hmthpy, and thpy, mthpy are the deprotonated forms of pyridoxal thiosemicarbazone and pyridoxal methylthiosemicarbazone, respectively; each is an O,N,S-tridentate ligand. The molecular structures have been determined at 100(1) K using single-crystal X-ray diffraction techniques and resulted in a triclinic system (space group P1) and monoclinic unit cell (space group P21/c) for 1 and 2, respectively. Structures were refined to the final error indices, where RF = 0.0560 for 1 and RF = 0.0522 for 2. The chemical inequivalence of the ligands was clearly established, for the "extra" hydrogen atom on the monodeprotonated ligands (Hthpy, Hmthpy) was found to be bound to the nitrogen of the pyridine ring. The ligands are all of the thiol form; the doubly deprotonated chelates (thpy, mthpy) have C-S bond lengths slightly longer than those of the singly deprotonated forms. There is a three-dimensional network of hydrogen bonds in both compounds. The discontinuous spin-state transformation is accompanied with liberation of solvate molecules. This is evidenced also from DSC analysis. Heat capacity data for the LS and HS phases are tabulated at selected temperatures, the values of the enthalpy and entropy changes connected with the change of spin state were reckoned at DeltaH = 12.5 0.3 kJ mol-1 and DeltaS = 33.3 0.8 J mol-1 K-1, respectively, for 1 and DeltaH = 6.5 0.3 kJ mol-1 and DeltaS = 17.6 0.8 J mol-1 K-1, respectively, for 2

Doing Relationships and Sexuality Education with Young People in State Care

Background: Existing literature indicates that young people in state carehave particular sexual health needs that include addressing their social andemotional well-being, yet little has been published as to how thesecomponents of sex education are actually delivered by service-providers.Objective: To analyse the processes involved in delivering relationship andsexuality education to young people in state care from the perspectives ofa sample of service-providers with a role in sexual health care delivery.Design: Qualitative methodological strategy.Setting: Service-delivery sites at urban and rural locations in Ireland.Method: Twenty-two service-providers were interviewed in depth, and datawere analysed using a qualitative analytical strategy resembling modifiedanalytical induction.Findings: Participants proffered their perceptions and examples of theirpractices of sex education in relation to the following themes: (1)acknowledging the multi-dimensional nature of sexual health in the case ofyoung people in care; (2) personal and emotional development educationto address poor self-esteem, emotional disconnectedness and an inabilityto recognise and express emotions; (3) social skills’ education as part of arepertoire of competencies needed to negotiate relationships and safer sex;(4) the application of positive social skills embedded in everyday socialsituations; and (5) factual sexuality education.Conclusion: Insights into service providers’ perceptions of the multidimensionalnature of the sexual health needs of young people in statecare, and the ways in which these service-providers justified their practicemake visible the complex character of sex education and the degree of skillrequired to deliver it to those in state care.